Heroin is an addictive drug and it has been very difficult to reduce heroin-seeking and -taking in
an animal model. Scientists at The Scripps Research Institute (TSRI) have found that
deep brain stimulation (DBS) can greatly reduce the compulsion to use
heroin in standard rat models of addiction.
Rats that were used to taking heroin, and normally would have
self-administered more and more of the drug, did not escalate their
intake when treated with DBS.
‘Deep brain stimulation (DBS) can greatly reduce the compulsion to use heroin in standard rat models of addiction.’
The treatment involves the weak electrical stimulation, via
implanted electrodes, of a brain region called the subthalamic nucleus.
The study's principal
investigator Olivier George, an associate professor in TSRI's Committee
on the Neurobiology of Addictive Disorders, said, "This is the type of
preclinical evidence that one needs, in order to start testing this
strategy in humans."
"These results also suggest new insights into the neurocircuitry of
heroin addiction," said co-author George F. Koob, who headed the
Committee during the study and is currently on leave from TSRI to direct
the National Institute on Alcohol Abuse and Alcoholism at the National
Institutes of Health.
DBS of the subthalamic nucleus is already used to treat symptoms of
Parkinson's disease and a separate movement disorder known as "essential
Scientists still don't fully understand what the subthalamic nucleus
does in the brain, but it apparently can modulate not only the abnormal
muscle activity of movement disorders, but also compulsive behaviors.
Researchers have noted, for example, that DBS of the subthalamic nucleus
in Parkinson's patients can reduce compulsive gambling and shopping.
2009, the FDA approved the use of subthalamic DBS for severe cases of
obsessive-compulsive disorder. Some recent studies in rodents have
suggested that DBS of this region can also reduce the motivation for
In the new study, published recently as an advance online paper in the journal Neuropsychopharmacology
George and his team used a model of heroin addiction in which rats are
allowed to self-administer heroin by pressing a lever, for 12 hours per
day over a two-week period. In this model, the rats normally increase
their intake and show various other signs of addiction. When their
access to the drug is restored after a two-week abstinence period, they
rapidly re-escalate their intake.
"It's like a human drug user who goes into rehab for two weeks, and
then comes back into the real world where he has access to the drug, and
starts taking more and more again," George said.
In the study, however, only the control rats who received no DBS
stimulation re-escalated their intake after the period of abstinence.
The DBS-treated rats kept their intake stable at a low level.
When the researchers switched off the DBS for two days, the treated
rats resumed a normal pattern of escalating heroin intake. "It was
really like an on-off switch," George said. "Then two days later we
turned it on again and their intake came back down."
In a second model in which rats are given shorter exposures to
heroin, DBS-treated animals again had significantly lower intakes
compared to untreated rats. Other experiments demonstrated that the
treated rats had markedly less motivation for heroin, giving up more
quickly when having to press a lever many times to obtain more of the
Overall the DBS-treated rats were just as active as control rats,
indicating that the treatment didn't work simply by reducing physical
Prior tests of the effects of DBS on compulsive behaviors have
generated conflicting results and interpretations. But George's team
examined measures of neuronal activity during DBS and concluded that the
treatment in this case worked by forcing a net reduction in the
activity of the subthalamic nucleus. Several regions that lie
"downstream" from the subthalamic nucleus also showed signs of reduced
activity with DBS treatment.
One of these regions is the nucleus accumbens shell, which is
involved in creating the senses of "liking" and "wanting" something
pleasurable, and has long been considered part of the brain circuitry
that maintains addiction. "It's interesting that with this new technique
we can actually inhibit the nucleus accumbens shell from a distance,"
"We think that deep brain stimulation can be a useful non-drug
intervention for treatment of addiction," added Carrie L. Wade, a
postdoctoral research associate in the George Laboratory during the
study, now at the University of Minnesota.
George noted that the intensity of the DBS used in the study was
much lower than what is used for treating movement disorders, and so is
unlikely to impair normal movement. "We think the low intensity of
stimulation will affect only the emotional, motivational part of the
subthalamic nucleus and not the part that's involved in controlling
muscle movements," George said.